title: Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.
abstract: OBJECTIVE
  The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied.
  
  
  METHODS
  European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants.
  
  
  RESULTS
  IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing.
  
  
  CONCLUSIONS
  Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.
authors.affiliation: Div. Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich Medical Centre, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rzehak
authors.forename: Veit
authors.initials: V
authors.lastname: Grote
authors.forename: Eva
authors.initials: E
authors.lastname: Lattka
authors.forename: Martina
authors.initials: M
authors.lastname: Weber
authors.forename: Dariusz
authors.initials: D
authors.lastname: Gruszfeld
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
authors.forename: Ricardo
authors.initials: R
authors.lastname: Closa-Monasterolo
authors.forename: Joaquín
authors.initials: J
authors.lastname: Escribano
authors.forename: Marcello
authors.initials: M
authors.lastname: Giovannini
authors.forename: Elvira
authors.initials: E
authors.lastname: Verduci
authors.forename: Philippe
authors.initials: P
authors.lastname: Goyens
authors.forename: Françoise
authors.initials: F
authors.lastname: Martin
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Langhendries
authors.forename: Hans
authors.initials: H
authors.lastname: Demmelmair
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
mesh_terms: D000367:Age Factors; D001942:Breast Feeding; D004435:Eating / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn / Q000254:growth & development; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics*; D008297:Male; D008894:Milk Proteins / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008894:Milk Proteins; D007334:Insulin-Like Growth Factor I
keywords: European Childhood Obesity Trial Study; IGF-1 gene; IGF-I concentration; IGFBP-3 variants; Protein formula; Randomized clinical trial